In this study, we aim to investigate the difference in the anabolic postprandial bile acid response between an enteral and parenteral mixed meal test (MMT) in healthy lean men. This study is important because it may give a better understanding of…
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess the effect of a parenteral MMT compared to an enteral MMT on
* Postprandial bile acid signalling metabolism
* Postprandial inflammatory responses
Secondary outcome
1. To assess the effect of a parenteral MMT compared to an enteral MMT on
* Glucoregulatory and gut hormones
* Lipid profiles
* Resting energy expenditure
* Appetite and satiety
* Blood pressure
* Body core temperature
2. Assess the correlation between the microbiota composition and postprandial
bile acid signalling.
Background summary
Total parenteral nutrition (TPN), a life-saving therapy, involves providing
nutrition while bypassing the gut. However, the clinical anabolic response to
TPN is less pronounced compared with enteral feeding. Also, TPN is associated
with significant complications including gut atrophy and parenteral nutrition
associated liver disease (PNALD), which includes steatosis, cholestasis,
disrupted glucose and lipid metabolism, cirrhosis, and liver failure. The
etiopathogenesis of PNALD remains poorly understood; however, emerging evidence
in animal studies suggests that inflammation and bile acid toxicity may
contribute to TPN related pathology.
Study objective
In this study, we aim to investigate the difference in the anabolic
postprandial bile acid response between an enteral and parenteral mixed meal
test (MMT) in healthy lean men. This study is important because it may give a
better understanding of the role of bile acids in TPN related pathology.
Moreover, we may find a potential therapeutic pathway to prevent or treat the
complications of TPN
Study design
The current study is an investigator initiated, single center, observational,
crossover study.
Intervention
Subjects will undergo an enteral and a parenteral mixed meal test (MMTs) on
different days in random order. The mixed meal test will be performed using
Olimel Perifeer N4E (Baxter B.V. Utrecht, The Netherlands), an emulsion for
parenteral nutrition containing a mix of glucose with calcium, a lipid emulsion
and an amino acid solution with other electrolytes. Before, during and after
the MMT, resting energy expenditure (REE) will be measured by indirect
calorimetry. Before the first MMT, subjects collect a morning stool sample at
home and bring it to the AMC. We will ask participants to fill in online or
written dietary diary for 3 days prior to the MMT to ensure the stability and
similarity of the gut microbiota. Core temperature will be measured with a body
core pill and blood pressure with Nexfin. After each MMT, appetite will be
evaluated with the Universal Eating Monitor.
Study burden and risks
Burden
The burden of this study includes a screening visit and 2x 7 hours admissions
to the hospital after an overnight fast including an enteral and parenteral MMT
with Olimel Perifeer N4E. Several blood samples will be drawn via an
intravenous cannula. The Olimel will be administered with a second intravenous
cannula (parenteral MMT) and a nasoduodenal tube (enteral MMT). The total
amount of blood taken will be 212 ml.
Risks
Olimel perifeer N4E (Baxter, Utrecht, The Netherlands) is registered for use as
the lipid component of total parenteral nutrition. Olimel Perifeer N4E is
specifically administered via a peripheral cannula (in contrast to central
venous catheters) because it has lower energetic density compared to other
lipid emulsions. The total lipid infusion in this study is therefore typically
low compared to standard daily dosing in patients (20% of total dose).
Insertion of an IV cannula carries the risk of hematoma or phlebitis.
The placement of nasoduodenal tube can lead to respiratory tract infection in
case of aspiration of gastric content. However, as subjects are fasted during
the placement, this is risk is very small.
Benefits
Subjects will not benefit from participation of this study.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
- Ability to provide informed consent
- 18 years or older at the time of signing the informed consent
- Body mass index (BMI) 18.5- 25 kg/m2
- Caucasian men
- General good health as determined by medical history, physical examination and blood chemistry by a physician.
-HOMA-IR index: * 2.0 (measured as fasting insulin (pmol/L) x fasting glucose (mmol/L) / 135)
Exclusion criteria
-Major illness in the past 3 months
-Use of any medication
-Gastro-intestinal disease that may influence bile acid metabolism
-History of cholecystectomy or other bile duct abnormalities
-Tobacco smoking
-Drugs abuse
-Alcoholism (>3 units a day)
-Allergy or intolerance to ingredients included in the standardized meals
-Blood chemistry:
*Creatinine >120 µM
*>2 times upper limit reference interval of the following: ASAT, ALAT, bilirubin, GGT and AF.
*Lipid spectrum
-Strenuous exercise for at least 3 days prior to each study day, defined as more than 1 hour of exercise per day.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL63468.018.17 |